Anti-oligomeric Abeta single-chain variable domain antibody blocks Abeta-induced toxicity against human neuroblastoma cells.
The Amyloid-beta (Abeta) peptide is a major component of the amyloid plaques associated with Alzheimer's disease (AD). Recent studies suggest that the most toxic forms of Abeta are small, soluble oligomeric aggregates. Here, we report the isolation and characterization of a single-chain variable domain (scFv) antibody isolated against oligomeric Abeta using a protocol developed in our laboratory that combines phage display technology and atomic force microscopy (AFM). Starting with a randomized, single framework phage display library, after three rounds of selection against oligomeric Abeta, we identified an scFv that bound oligomeric Abeta specifically, but not monomeric or fibrillar forms. The anti-oligomeric scFv inhibits Abeta aggregation and toxicity, and reduces the toxicity of preformed oligomeric Abeta towards human neuroblastoma cells. When used to probe samples of human brain tissue, the scFv reacted with AD tissue but not a healthy control or Parkinson's disease brain samples. The anti-oligomeric Abeta scFv therefore has potential therapeutic and diagnostic applications in specifically targeting or identifying the toxic morphologies of Abeta in AD brains.
Zameer
Andleeb
A
Department of Chemical Engineering, Arizona State University, Tempe, AZ 85287, USA.
Kasturirangan
Srinath
S
Emadi
Sharareh
S
Nimmagadda
Sridevi V
SV
Sierks
Michael R
MR
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000906:Antibodies / Q000276:immunology* / Q000302:isolation & purification*; D001921:Brain / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D018625:Microscopy, Atomic Force; D019151:Peptide Library
D016229:Amyloid beta-Peptides; D000906:Antibodies; D019151:Peptide Library